NEURO-COGS: Neurometabolic Mechanisms of Cognitive Training in Schizophrenia

NCT07788755 | Not Yet Recruiting FDA Device

• 2 other identifiers: PSYCH-2026-3487734877
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine brain metabolic and excitatory/inhibitory mechanisms related to cognitive and visual functioning in adults with schizophrenia and healthy control participants. Participants will complete behavioral assessments, cognitive testing, electroencephalography, magnetic resonance imaging, and magnetic resonance spectroscopy assessments. After baseline assessments, participants will be randomly assigned to one of two computerized cognitive training programs: perceptual discrimination training or cognitive control training. Each training program will include approximately 10 hours of training over 2 to 6 weeks. The study will evaluate changes in cognitive and visual task performance, EEG measures, and brain metabolite concentrations before and after cognitive training. Some participants may also complete optional extended baseline assessments before cognitive training.

Conditions

Cognitive Impairment; Schizophrenia; Schizoaffective Disorder; Visual Impairment

Keywords

NEURO-COGS; Schizophrenia; Cognitive training; Schizoaffective disorder; BrainHQ; Perceptual discrimination training; Brain metabolism

Outcome Measures

Primary Outcomes (3)

• Change in DPX Task Performance

  Behavioral performance on the DPX task variant will be assessed as a measure of cognitive control. Trial-by-trial behavioral data will be used to derive observed behavioral and computational metrics of cognitive control. The DPX task variant consists of a series of pattern sequences. One pattern is designated the "A" cue followed by the "X" cue, which requires one response (AX, 60-70% of trials, e.g. respond with the left button), while other pattern sequences require a different response (AY or BX, 12-15% of trials each, or BY, 6-10% of trials, e.g. respond with the right button). Given the strong expectation that X's evoke a valid response, BX trials place demands on cognitive control via the fidelity (stability, memory) of the "B" cue representation to overcome this tendency. Unit of Measure: Mean and standard deviation for BX trial error rate

  Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component

• Number of participants with pre/post EEG data

  The final sample size (participants with resting electroencephalography before and after intervention) will be reported to facilitate future analyses of change in EEG variables, which could include phase synchrony, slope of the spectral power density indexing excitatory/inhibitory balance, and/or prefrontal/parietal theta as a measure of perceptual noise. Units of Measure: Number of participants with pre/post EEG data

  Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component

• Number of participants with pre/post Magnetic Resonance Spectroscopy data

  Magnetic resonance spectroscopy (MRS) will be used to measure neurometabolite concentrations, including but not limited to glutamate, GABA, glutathione, and glucose. MRS measurements will be collected from prefrontal and occipital cortex. The final sample size (participants with MRS before and after intervention) will be reported to facilitate future analyses of change in MRS variables. Units of Measure: Number of participants with pre/post MRS data

  Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component

Secondary Outcomes (5)

• Change in Brief Psychiatric Rating Scale Score

  Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component

• Change in Positive Symptom Scores

  Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component

• Change in Negative Symptom Scores

  Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component

• Change in World Health Organization Disability Assessment Schedule Score

  Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component

• Change in Global Functioning Role Scale Score

  Baseline to post-training follow-up, up to 7 months; or baseline to post-training follow-up, up to 42 months for participants completing the optional extended baseline component

Study Arms (2)

Perceptual Discrimination Training

EXPERIMENTAL

Participants randomized to this arm will complete computerized perceptual discrimination training. The training involves Gabor patch and other visual stimulus discrimination exercises designed to improve signal-to-noise resolution and attentional control. Participants will complete approximately 10 hours of training over 2 to 6 weeks.

Device: Perceptual Discrimination Training

Cognitive Control Training

EXPERIMENTAL

Participants randomized to this arm will complete computerized cognitive control training. The training involves exercises focused on maintaining cognitive context in working memory during response selection. Participants will complete approximately 10 hours of training over 2 to 6 weeks.

Device: Cognitive Control Training

Interventions

Perceptual Discrimination Training DEVICE

Perceptual discrimination training is a computerized cognitive training program delivered through the BrainHQ platform. Training involves Gabor patch and other visual stimulus discrimination exercises that focus on improving signal-to-noise resolution and attentional control. On each training trial, participants distinguish a target stimulus among distractor stimuli. Training difficulty adapts based on participant performance. Participants complete approximately 10 hours of training over 2 to 6 weeks.

Also known as: BrainHQ Perceptual Discrimination Training

Perceptual Discrimination Training

Cognitive Control Training DEVICE

Cognitive control training is a computerized cognitive training program delivered through the BrainHQ platform. Training involves maintaining accurate representations of cognitive context in working memory during response selection. Training difficulty adapts based on participant performance by changing the speed of stimulus presentation or working memory load. Participants complete approximately 10 hours of training over 2 to 6 weeks.

Also known as: BrainHQ Cognitive Control Training

Cognitive Control Training

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants (healthy control and SZ):
• Age: 18-79
• Have given written informed consent
• Be able to read and write in English
• General health status: Participants should be in good general physical health (no major neurological disorder or head injury with prolonged unconsciousness, and no current moderate or severe substance use disorder)
• Geographic location: Minnesota counties that are approximately within 1 hour driving distance to Twin Cities, including, but not limited to, Hennepin, Ramsey, Washington, Anoka, Wright, Carver, Scott, Dakota, Sherburn
• Agree to refrain from using recreational drugs for 1 week prior to each scanning session, including, but not limited to, marijuana
• For people with schizophrenia (SZ):
• Current DSM-5 diagnosis of schizophrenia or schizoaffective disorder. Participants should be in stable psychiatric health, evidenced by no suicide attempt or psychiatric hospitalization within the past 1 month. (Initial diagnosis will be assessed using SCID 5 or MINI-7, and confirmation of ongoing SZ status and symptom changes will be monitored at each major timepoint using BPRS.)
• All SZ must have achieved clinical stability, defined as outpatient status for at least one month prior to study participation, plus stable doses of psychiatric medications for at least 1 month prior to study participation (as reported by participants and confirmed via medication list (procured by participants via their own medical or pharmacy records) and/or current pill bottle labels).
• All participants should have symptom ratings below a rating of 7 "extremely severe" on a severity scale of 1-7 on the BPRS and/or below grade 3 on longitudinal assessment defined by (as determined by the PI):
• Grade 1: Worsening of 1 point on any item within each BPRS factor
• Grade 2: Worsening of 2 points on any item within each BPRS factor
• Grade 3: Worsening of 3+ points on any item within each BPRS factor, or a change to a rating of extremely severe
• Grade 4: Suicide attempt with intent to die

You may not qualify if:

• Presence of major neurological disorder
• Conditions preventing MR scanning or other MRI contraindications:
• Implanted devices or ferromagnetic objects, current pregnancy (positive pregnancy test on day of MRI scanning or currently breast-feeding), etc. Significant movement disorders including tardive dyskinesia that could disrupt MRI and MRS recordings. Medically significant condition considered unsuitable for the current study (e.g., epilepsy, etc.)
• Estimated IQ \< 70
• Other relevant comorbidity (e.g., epilepsy, developmental disability) or visual impairment
• Presence of current substance use disorder (moderate or severe; excluding caffeine and nicotine), as measured by the MINI-7 or SCID 5 based on DSM-5 criteria.
• For healthy controls, additionally:
• Personal or immediate first-degree family history of a psychotic or mood disorder. Specifically, current or past history of meeting DSM-5 criteria for schizophrenia spectrum or other psychotic disorders, or Bipolar I or II Disorder, major depressive disorder, posttraumatic stress disorder, panic disorder, obsessive compulsive disorder, dysthymic disorder. Those with a first or second-degree relative with a current or past history of meeting DSM-5 criteria for schizophrenia or other psychotic disorders or bipolar I or II disorder, because they might have an underlying genetic susceptibility for psychosis symptoms.
• Presence of symptoms of the following DSM-5 disorders (as assessed by the MINI-7 or SCID 5):
• Major Depressive Episode
• Suicidality
• Manic and Hypomanic Episodes
• Panic disorder
• Obsessive-Compulsive Disorder
• Posttraumatic Stress Disorder

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

Center for Magnetic Resonance Research, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Cognitive Dysfunction; Vision Disorders

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Caroline Demro, PhD, LP

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Caroline Demro, PhD, LP

CONTACT

612-625-3330; schi0599@umn.edu

Claire McDonald

CONTACT

mcdo1202@umn.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study. Participants and study staff will know which computerized cognitive training intervention is assigned.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomly assigned to one of two computerized cognitive training interventions: perceptual discrimination training or cognitive control training. Both training programs include approximately 10 hours of training delivered over a 2- to 6-week period.

Study Record Dates

• First Submitted: July 31, 2026
• First Posted: August 26, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2031
• Last Updated: August 26, 2026

Record last verified: 2026-08

Locations

US (1)